tbuckley/cabot-search huggingface dataset:
Feasibility of measles and rubella vaccination programmes for disease elimination: a modelling study
Authors: Amy K Winter, Brian Lambert, Daniel Klein, Petra Klepac, Timos Papadopoulos, Shaun Truelove, Colleen Burgess, Heather Santos, Jennifer K Knapp, Susan E Reef, Lidia K Kayembe, Stephanie Shendale, Katrina Kretsinger, Justin Lessler, Emilia Vynnycky, Kevin McCarthy, Matthew Ferrari, Mark Jit
Journal: The Lancet Global Health (2022)

Marked reductions in the incidence of measles and rubella have been observed since the widespread use of the measles and rubella vaccines. Although no global goal for measles eradication has been established, all six WHO regions have set measles elimination targets. However, a gap remains between current control levels and elimination targets, as shown by large measles outbreaks between 2017 and 2019. We aimed to model the potential for measles and rubella elimination globally to inform a WHO report to the 73rd World Health Assembly on the feasibility of measles and rubella eradication.In this study, we modelled the probability of measles and rubella elimination between 2020 and 2100 under different vaccination scenarios in 93 countries of interest. We evaluated measles and rubella burden and elimination across two national transmission models each (Dynamic Measles Immunisation Calculation Engine [DynaMICE], Pennsylvania State University [PSU], Johns Hopkins University, and Public Health England models), and one subnational measles transmission model (Institute for Disease Modeling model). The vaccination scenarios included a so-called business as usual approach, which continues present vaccination coverage, and an intensified investment approach, which increases coverage into the future. The annual numbers of infections projected by each model, country, and vaccination scenario were used to explore if, when, and for how long the infections would be below a threshold for elimination.The intensified investment scenario led to large reductions in measles and rubella incidence and burden. Rubella elimination is likely to be achievable in all countries and measles elimination is likely in some countries, but not all. The PSU and DynaMICE national measles models estimated that by 2050, the probability of elimination would exceed 75% in 14 (16%) and 36 (39%) of 93 modelled countries, respectively. The subnational model of measles transmission highlighted inequity in routine coverage as a likely driver of the continuance of endemic measles transmission in a subset of countries.To reach regional elimination goals, it will be necessary to innovate vaccination strategies and technologies that increase spatial equity of routine vaccination, in addition to investing in existing surveillance and outbreak response programmes.WHO, Gavi, the Vaccine Alliance, US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation.
Interplay between aging and other factors of the pathogenesis of age-related macular degeneration
Authors: Janusz Blasiak, Piotr Sobczuk, Elzbieta Pawlowska, Kai Kaarniranta
Journal: Ageing Research Reviews (2022)

Age-related macular degeneration (AMD) is a complex eye disease with the retina as the target tissue and aging as per definition the most serious risk factor. However, the retina contains over 60 kinds of cells that form different structures, including the neuroretina and retinal pigment epithelium (RPE) which can age at different rates. Other established or putative AMD risk factors can differentially affect the neuroretina and RPE and can differently interplay with aging of these structures. The occurrence of β-amyloid plaques and increased levels of cholesterol in AMD retinas suggest that AMD may be a syndrome of accelerated brain aging. Therefore, the question about the real meaning of age in AMD is justified. In this review we present and update information on how aging may interplay with some aspects of AMD pathogenesis, such as oxidative stress, amyloid beta formation, circadian rhythm, metabolic aging and cellular senescence. Also, we show how this interplay can be specific for photoreceptors, microglia cells and RPE cells as well as in Bruch's membrane and the choroid. Therefore, the process of aging may differentially affect different retinal structures. As an accurate quantiﬁcation of biological aging is important for risk stratiﬁcation and early intervention for age-related diseases, the determination how photoreceptors, microglial and RPE cells age in AMD may be helpful for a precise diagnosis and treatment of this largely untreatable disease.
Peroral endoscopic myotomy after transjugular intrahepatic portosystemic shunt and variceal embolization for a patient with achalasia and esophageal varices
Authors: Wenjuan Yang, Liansong Ye, Chengwei Tang, Bing Hu, Zhe Feng
Journal: Endoscopy (2022)

A 54-year-old woman with achalasia was referred to our hospital for peroral endoscopic myotomy (POEM). She complained of dysphagia, regurgitation, vomiting, chest pain, and a weight loss of 10 kg in the past two years. Her body mass index was 17.03 kg/m2. She was diagnosed with hepatitis B-related cirrhosis 2 years earlier. Esophagram showed a dilated esophagus with a significant delay of barium passing ([Fig. 1]). Endoscopy showed an obvious dilated esophagus and persistently closed cardia with varices in the lower esophagus ([Fig. 2]). Abdominal computed tomography (CT) angiography detected liver cirrhosis and gastroesophageal varices ([Fig. 3]). Considering the high risk of bleeding during POEM, a transjugular intrahepatic portosystemic shunt (TIPS) and variceal embolization were implemented with the patient's informed consent, after which the portal venous pressure gradient was reduced from 16 mmHg to 8 mmHg, and gastroesophageal varices also disappeared under angiography. Endoscopy after 2 months confirmed that the esophageal varices were no longer visible ([Fig. 4]), and therefore the POEM procedure was performed ([Video 1]). During the procedure, several blood vessels were still encountered ([Fig. 5]), but they were easily treated using high frequency electrocoagulation. After the POEM procedure, the patient's symptoms obviously improved. The patient was doing well at her 1-year follow-up.
Epidemiology of peritoneal dialysis outcomes
Authors: Aminu K. Bello, Ikechi G. Okpechi, Mohamed A. Osman, Yeoungjee Cho, Brett Cullis, Htay Htay, Vivekanand Jha, Muhammad A. Makusidi, Mignon McCulloch, Nikhil Shah, Marina Wainstein, David W. Johnson
Journal: Nature Reviews Nephrology (2022)
Site‐Specific Polyplex on CCR7 Down‐Regulation and T Cell Elevation for Lymphatic Metastasis Blocking on Breast Cancer
Authors: Yueyang Deng, Caixia Tan, Shuguang Huang, Honghao Sun, Zhaoting Li, Jing Li, Zhanwei Zhou, Minjie Sun
Journal: Advanced Healthcare Materials (2022)

Abstract Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration. Here, a site‐specific polyplex is developed to block the CCR7‐CCL21 signal and kill tumor cells toward LNs, greatly limiting their lymphatic infiltration. A CCR7‐targeting small interfering RNA (siCCR7) is condensed by mPEG‐poly‐(lysine) with chlorin e6 (Ce6) modification (PPLC) to form PPLC/siCCR7. The knockdown of CCR7 by siCCR7 in tumor cells significantly reduced their response on CCL21 and LN tropism. Additionally, photodynamic therapy‐mediated immune activation precisely targets and kills tumor cells released from the primary foci before they reaches the LNs, reducing the number of tumor cells entering the LNs. Consequently, the PPLC/siCCR7 polyplexes inhibited up to 92% of lung metastasis in 4T1 tumor bearing mice and reduced tumor cell migration to LNs by up to 80%. This site‐specific strategy optimized anti‐metastasis efficacy and promotes the clinical translational development of anti‐metastatic therapy.
Ligands stimulating antitumour immunity as the next G-quadruplex challenge
Authors: Giulia Miglietta, Jessica Marinello, Marco Russo, Giovanni Capranico
Journal: Molecular Cancer (2022)

Abstract G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effective in cancer patients. Here, G4 binder activity at low dosages will be discussed as a critical feature to discover ligands with therapeutic effects in cancer patients. Specific effects of G4 binders al low doses have been reported to occur in cancer and normal cells. Among them, genome instability and the stimulation of cytoplasmic processes related to autophagy and innate immune response open to the use of G4 binders as immune-stimulating agents. Thus, we propose a new rational of drug discovery, which is not based on cytotoxic potency but rather on immune gene activation at non-cytotoxic dosage.
Dermatology evaluation for cutaneous immune-related adverse events is associated with improved survival in cancer patients treated with checkpoint inhibition
Authors: Ted V. Jacoby, Nishi Shah, Maria S. Asdourian, Leah L. Thompson, Tracey S. Otto, Nicole R. LeBoeuf, Yevgeniy Semenov, Edward Christopher Dee, Kerry L. Reynolds, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2022)
Use of a bougie-shaped cap for dilation with direct visual control for an esophageal stricture induced by radiation therapy
Authors: Pierre Lafeuille, Clara Yzet, Paul Bonniaud, Florian Rostain, Thierry Ponchon, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2022)

Bougies and balloons are two instruments commonly used for endoscopic dilation of benign strictures in the upper gastrointestinal tract, with similar efficacy [1]. However, these invasive strategies do not allow visual control of the operation during dilation of the stricture, and bleeding caused by the treatment itself prevents proper examination of the esophageal mucosa after the procedure. The BougieCap (Ovesco, Tübingen, Germany) is a recently developed dilation device that allows successful and safe endoscopic treatment of benign strictures [2].
Ethnoracial inequalities and child mortality in Brazil: a nationwide longitudinal study of 19 million newborn babies
Authors: Poliana Rebouças, Emanuelle Goes, Julia Pescarini, Dandara Ramos, Maria Yury Ichihara, Samila Sena, Rafael Veiga, Laura C Rodrigues, Maurício L Barreto, Enny S Paixão
Journal: The Lancet Global Health (2022)
HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling
Authors: Ihor Arkhypov, Feyza Gül Özbay Kurt, Rebekka Bitsch, Daniel Novak, Vera Petrova, Samantha Lasser, Thomas Hielscher, Christopher Groth, Alisa Lepper, Xiaoying Hu, Wei Li, Jochen Utikal, Peter Altevogt, Viktor Umansky
Journal: Journal for ImmunoTherapy of Cancer (2022)

Tumor cells modulate host immunity by secreting extracellular vesicles (EV) and soluble factors. Their interactions with myeloid cells lead to the generation of myeloid-derived suppressor cells (MDSC), which inhibit the antitumor function of T and NK cells. We demonstrated previously that EV derived from mouse and human melanoma cells induced immunosuppressive activity via increased expression of programmed cell death ligand 1 (PD-L1) on myeloid cells that was dependent on the heat-shock protein 90α (HSP90α) in EV. Here, we investigated whether soluble HSP90α could convert monocytes into MDSC.
Amplifying the global issue of hearing loss
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2022)

Hearing aids will soon become available directly from retailers for adults with mild to moderate hearing loss in the USA, thanks to a long-awaited Food and Drug Administration rule that establishes a new category of over-the-counter (OTC) hearing aids. The agency's announcement emphasised the expectation that the legislation would lower the price of hearing aids without sacrificing their safety and effectiveness. This overdue move represents a welcome step forward for people with hearing loss in the USA, and should provide impetus for the global community to address what is often a neglected disability.
Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial
Authors: Kathy Baisley, Troy J Kemp, Aimée R Kreimer, Partha Basu, John Changalucha, Allan Hildesheim, Carolina Porras, Hilary Whitworth, Rolando Herrero, Charles J Lacey, John T Schiller, Eric Lucas, Paul Mutani, Joakim Dillner, Jackton Indangasi, Richard Muwonge, Richard J Hayes, Ligia A Pinto, Deborah Watson-Jones
Journal: The Lancet Global Health (2022)

Human papillomavirus (HPV) vaccines are given as a two-dose schedule in children aged 9-14 years, or as three doses in older individuals. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), a randomised trial of different HPV vaccine schedules in Tanzania, to those from two observational HPV vaccine trials that found high efficacy of one dose up to 11 years against HPV16 and HPV18 (Costa Rica Vaccine Trial [CVT] and Institutional Agency for Research on Cancer [IARC] India trial).
Diagnostic accuracy of covid-19 rapid antigen tests with unsupervised self-sampling in people with symptoms in the omicron period: cross sectional study
Journal: BMJ (2022)

Diagnostic accuracy of covid-19 rapid antigen tests with unsupervised self-sampling in people with symptoms in the omicron period: cross sectional studyIn this paper by Schuit and colleagues (BMJ 2022;378:e071215, doi:, published
Reply to Joanne L. Dickinson, Georgea R. Foley, and Liesel M. FitzGerald’s Letter to the Editor re: Daniel J. Lee, Ryan Hausler, Anh N. Le, et al. Association of Inherited Mutations in DNA Repair Genes with Localized Prostate Cancer. Eur Urol 2022;81:559–67. Red Flags in Association Analyses for Rare Variants
Authors: Daniel J Lee, Ryan Hausler, Kara N Maxwell
Journal: European Urology (2022)
Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study
Authors: Gabriel A Gregory, Thomas I G Robinson, Sarah E Linklater, Fei Wang, Stephen Colagiuri, Carine de Beaufort, Kim C Donaghue, Dianna J Magliano, Jayanthi Maniam, Trevor J Orchard, Priyanka Rai, Graham D Ogle, Jessica L Harding, Pandora L Wander, Xinge Zhang, Xia Li, Suvi Karuranga, Hongzhi Chen, Hong Sun, Yuting Xie, Richard Oram, Dianna J Magliano, Zhiguang Zhou, Alicia J Jenkins, Ronald CW Ma
Journal: The Lancet Diabetes & Endocrinology (2022)
MEX3C-Mediated Decay of SOCS3 mRNA Promotes JAK2/STAT3 Signaling to Facilitate Metastasis in Hepatocellular Carcinoma
Authors: Yunyun Xiao, Yue Li, Dongni Shi, Xiaoqing Wang, Shuqin Dai, Muwen Yang, Lingzhi Kong, Boyu Chen, Xinjian Huang, Chuyong Lin, Wenting Liao, Benke Xu, Xin Chen, Lishuai Wang, Xiangfu Chen, Ying Ouyang, Guozhen Liu, Heping Li, Libing Song
Journal: Cancer Research (2022)

Abstract Tumor metastasis is one of the major causes of high mortality in patients with hepatocellular carcinoma (HCC). Sustained activation of STAT3 signaling plays a critical role in HCC metastasis. RNA binding protein (RBP)–mediated posttranscriptional regulation is involved in the precise control of signal transduction, including STAT3 signaling. In this study, we investigated whether RBPs are important regulators of HCC metastasis. The RBP MEX3C was found to be significantly upregulated in highly metastatic HCC and correlated with poor prognosis in HCC. Mechanistically, MEX3C increased JAK2/STAT3 pathway activity by downregulating SOCS3, a major negative regulator of JAK2/STAT3 signaling. MEX3C interacted with the 3′UTR of SOCS3 and recruited CNOT7 to ubiquitinate and accelerate decay of SOCS3 mRNA. Treatment with MEX3C-specific antisense oligonucleotide significantly inhibited JAK2/STAT3 pathway activation, suppressing HCC migration in vitro and metastasis in vivo. These findings highlight a novel mRNA decay-mediated mechanism for the disruption of SOCS3-driven negative regulation of JAK2/STAT3 signaling, suggesting MEX3C may be a potential prognostic biomarker and promising therapeutic target in HCC. Significance: This study reveals that RNA-binding protein MEX3C induces SOCS3 mRNA decay to promote JAK2/STAT3 activation and tumor metastasis in hepatocellular carcinoma, identifying MEX3C targeting as a potential approach for treating metastatic disease.
Paraskeletal and extramedullary plasmacytomas in multiple myeloma at diagnosis and at first relapse: 50-years of experience from an academic institution
Authors: Raquel Jiménez-Segura, Laura Rosiñol, Ma Teresa Cibeira, Carlos Fernández de Larrea, Natalia Tovar, Luis Gerardo Rodríguez-Lobato, Esther Bladé, David F. Moreno, Aina Oliver-Caldés, Joan Bladé
Journal: Blood Cancer Journal (2022)

From January 1970 to December 2018, 1304 patients were diagnosed with multiple myeloma (MM) at our institution and 256 (19.6%) had plasmacytomas (Ps) (paraskeletal -PPs- 17.6%, extramedullary -EMPs-1.9%). Patients with Ps had lower serum M-protein and less advanced ISS stage than those without. At first relapse, 192 out of 967 patients (19.8%) developed Ps (PPs 14.6%, EMPs 5.1%). The only factor associated with Ps at relapse was the presence of Ps at diagnosis (46% vs 13%, p < 0.00001) with no impact with exposure to novel drugs or previous autologous stem-cell transplantation (ASCT). The median overall survival (OS) was 45, 44 and 20 months for patients without Ps, PPs and EMPs, respectively (p = 0.013). Patients with PPs who underwent ASCT had similar OS than those without Ps (98 vs. 113 months) and significantly longer than those with EMPs (98 vs 47 months, p = 0.006). In patients non-eligible for ASCT the presence of PPs or EMPs was associated with shorter OS compared with patients without Ps (32 vs. 24 vs. 6 months, p = 0.009). In the relapsed setting, a significant survival benefit was observed beyond the year 2000, but still with significant differences among patients without Ps, PPs and EMPs (37 vs 22 vs 16 months, p = 0.003). Importantly, rescue therapy with combinations of proteasome-inhibitors plus immunomodulatory drugs was associated with prolonged OS from first relapse (over 6 years), even in patients with EMPs.
iPLAT1: the first-in-human clinical trial of iPSC-derived platelets as a phase 1 autologous transfusion study
Authors: Naoshi Sugimoto, Junya Kanda, Sou Nakamura, Toshiyuki Kitano, Masakatsu Hishizawa, Tadakazu Kondo, Shin Shimizu, Akiko Shigemasa, Hideyo Hirai, Yasuyuki Arai, Manabu Minami, Harue Tada, Dai Momose, Ki-Ryang Koh, Masayuki Nogawa, Naohide Watanabe, Shinichiro Okamoto, Makoto Handa, Akira Sawaguchi, Nobuki Matsuyama, Mitsunobu Tanaka, Tomoya Hayashi, Akihiro Fuchizaki, Yoshihiko Tani, Akifumi Takaori-Kondo, Koji Eto
Journal: Blood (2022)

Refractoriness to platelet transfusion is a major problem in a small group of patients, and large-scale manufacturing of clinical grade functional platelets ex vivo has remained an elusive goal. Sugimoto et al report on the results of the first clinical trial of an autologous transfusion of induced pluripotent stem cell (iPSC)-derived platelets in a patient who had severe aplastic anemia but no compatible platelet donor. Using methodology described in a complementary article in Blood Advances, the results provide proof-of-principle and illustrate the challenges to be faced in taking this approach further.
Characteristics and clinical outcomes of patients with acute heart failure with a supranormal left ventricular ejection fraction
Authors: Bart J. van Essen, Jasper Tromp, Jozine M. ter Maaten, Barry H. Greenberg, Claudio Gimpelewicz, G. Michael Felker, Beth A. Davison, Thomas Severin, Peter S. Pang, Gad Cotter, John R. Teerlink, Marco Metra, Adriaan A. Voors
Journal: European Journal of Heart Failure (2022)

Abstract Aim Recent data suggest that guideline‐directed medical therapy of patients with heart failure (HF) with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with HF up to a left ventricular ejection fraction (LVEF) of 55–65%, whereas patients with higher LVEF do not seem to benefit. Recent data have shown that LVEF may have a U‐shaped relation with outcome, with poorer outcome also in patients with supranormal values. This suggests that patients with supranormal LVEF may be a distinctive group of patients. Methods and results RELAX‐AHF‐2 was a multicentre, placebo‐controlled trial on the effects of serelaxin on 180‐day cardiovascular (CV) mortality and worsening HF at day 5 in patients with acute HF. Echocardiograms were performed at hospital admission in 6128 patients: 155 (2.5%) patients were classified as HF with supranormal ejection fraction (HFsnEF; LVEF &gt;65%), 1440 (23.5%) as HF with preserved ejection fraction (HFpEF; LVEF 50–65%), 1353 (22.1%) as HF with mildly reduced ejection fraction (HFmrEF; LVEF 41–49%) and 3180 (51.9%) as HFrEF (LVEF &lt;40%). Patients with HFsnEF compared to HFpEF were more often women, had higher prevalence of non‐ischaemic HF, had lower levels of natriuretic peptides, were less likely to be treated with beta‐blockers and had higher blood urea nitrogen plasma levels. All‐cause mortality was not statistically different between groups, although patients with HFsnEF had the highest numerical rate. A declining trend was seen in the proportion of 180‐day deaths due to CV causes from HFrEF (290/359, 80.8%) to HFsnEF (14/24, 58.3%). The reverse was observed with death from non‐CV causes. No treatment effect of serelaxin was observed in any of the subgroups. Conclusions In this study, only 2.5% of patients were classified as HFsnEF. HFsnEF was primarily characterized by female sex, lower natriuretic peptides and a higher risk of non‐CV death.